Dopamine systems are intimately involved with opioid actions. Pharmacological studies suggest an important modulatory effect of dopamine and its receptors on opioid analgesia. We have now examined these interactions in a knock-out model in which the dopamine(2) (D(2)) receptor has been disrupted. Loss of D(2) receptors enhances, in a dose-dependent manner, the analgesic actions of the mu analge...

C appreciate that there is interplay between the actions of the different subtypes of receptor and hence the value of drugs which target multiple receptor subtypes. Abstract The opioid system comprises four receptor subtypes: m (MOP), k (KOP), d (DOP), now called the ‘classical’ opioid receptors, and the ‘non classical’ nociceptin/orphanin FQ peptide (N/OFQ) receptor (NOP). Selective endogenous...

Respiratory depression is a therapy-limiting side effect of opioid analgesics, yet our understanding of the brain circuits mediating this potentially lethal outcome remains incomplete. Here we studied the contribution of the rostral ventromedial medulla (RVM), a region long implicated in pain modulation and homeostatic regulation, to opioid-induced respiratory depression. Microinjection of the ...

Attitudinal barriers towards analgesic use among primary care patients with chronic pain and substance use disorders (SUDs) are not well understood. We evaluated the prevalence of moderate to significant attitudinal barriers to analgesic use among 597 primary care patients with chronic pain and current analgesic use with 3 subscales from the Barriers Questionaire II: concern about side effects,...

BACKGROUND Interindividual variability in pain perception and analgesic response is a major problem in perioperative practice. Adult studies suggest pain management is influenced by patient's race. The objective of this study is to evaluate the influence of race on perioperative pain treatment in children. METHODS Prospective observational study evaluating effect of race on analgesia and opio...

Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation ...

To elucidate mechanisms of acute and chronic pain, it is important to understand how spinal excitatory systems influence opioid analgesia. The tachykinin substance P (SP) represents the prototypic spinal excitatory peptide neurotransmitter/neuromodulator, acting in concert with endogenous opioid systems to regulate analgesic responses to nociceptive stimuli. We have synthesized and pharmacologi...

Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the μ opioid receptor. In addition to being a potent μ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analg...

An association between non-opioid analgesic agents and chronic kidney disease has long been suspected. The presumed development of chronic renal impairment following protracted excessive use of non-opioid analgesia is known as analgesic nephropathy. Many accept analgesic nephropathy as a real entity despite a paucity of robust scientific evidence. The weight of available observational literatur...